Causes & Treatment

Fertility Help – Everything You Need to Know About Immunology and Fertility by IVF Spain

Eloise Edington  |   15 Mar 2020

Here at The Ribbon Box, we’re all about asking the experts things you want and need to know more about. When we recently did a poll of suggested topics, what came up trumps was Immunology and the effect of it on fertility / understanding more about how it can be treated.

So we’ve chatted with the fantastic team at IVF Spain – the inspiring Dr Rogel answers your questions…

What is immunology and how is it connected to fertility?

We could define Immunology as the branch of medicine that studies the functioning of the immune system. It diagnoses multiple possible pathologies and takes care of their treatment. This area of knowledge is the object of a whole important medical specialty (there are doctors who dedicate their lives to the study and treatment of problems related to the immune system).

In recent years there have been many advances in different fields of reproductive medicine. However, there are patients who, despite having a superb embryo, a uterus without pathology, normal endometrial receptivity, absence of hypercoagulability or other alterations, present miscarriages or implantation failures that are difficult to explain. That is why reproductive medicine has sought answers in immunology. After all, the transfer of one or more embryos is nothing more than the implantation of a material that is at least 50% genetically and immunologically different from the woman. Thus, from this incipient collaboration between two branches of medicine, different possible pathologies have been discovered that can affect pregnancy and there are many others that are still in the research stage.

If you suspect you have an immune condition that is affecting the outcome of your fertility treatments, what would you advise doing next?

The best would be to do the Im Map test, also called Immnulogical Map, which is performed on an endometrial biopsy in the luteal phase and a blood sample for following up with an immunotherapy. Afterwards the samples are analysed under a flow cytometer, a biophysical technology employed to detect immunological markers and cell counting.  If there are any abnormal levels of immune cells detected, the right immune therapy suited to each patient can be offered.

Does Rheumatoid Arthritis have a negative impact on fertility?

Specific autoimmune diseases entail states of activation of the inflammatory response that seem to affect fertility and trying to conceive, mainly in women, by little known mechanisms, in which the activation of the inflammatory response, a lower quality of oocyte, less mobility of the fallopian tubes, alteration of the embryonic implantation process, etc. are probably involved. In addition, some of the drugs used in this pathology can produce teratogen (foetal malformations) or a lower probability of implantation.

Immune Testing Before the First FET

Should you do immune testing before the first FET (Frozen Embryo Transfer)?

No. The probability of a patient presenting an immune problem when not even an embryo transfer has been performed yet is very low, so immunological tests should not be performed in these cases. This statement focuses on two important medical principles: the first is the proportionality of the cost-benefit. Every test and subsequent treatment has its cost (and in the case of immunology this is not usually small). At this point it should be noted that cost is not only considered in economic terms, but also in terms of possible short-, medium- and long-term side effects.  The second and perhaps most important principle is that of test effectiveness. Every test, absolutely every test, in medicine will have false positives and false negatives, which depend on the probability of finding a sick person in the studied population. For example, if we use, say, a test that detects a sexually transmitted disease in a convent of cloistered nuns, the likelihood is that a positive result will simply be false. Similarly, if we use tests designed to detect immune diseases in healthy patients it is more than likely that we are over-diagnosing immune pathology. In other words, medical tests should be based on a previous clinical situation, so in the case of immunological tests they should be performed in cases of suspected pathology, usually in cases of implantation failure or repeated miscarriages.

What other tests do you recommend for miscarriages and repeated implantation failures?

I don’t know what you mean by “other” but I will describe a bit what is done after implantation failure.

The first thing we should think about when we have implantation failures or repeated miscarriages is possible genetic failures in the embryos, which will lead us to advise the performance of karyotypes in the parents (both) and Preimplantation Genetic Diagnosis of Aneuploidy (PGT-a), formerly called PGS.

Other classic causes of implantation failure and repeated miscarriage are coagulation problems: lupus anticoagulant, antiphospholipid antibodies, coagulation protein C and S, AT-III

Anatomical alterations such as hydro salpinx or uterine alterations may be the cause of this type of problem (special ultrasound scans, 3-D Doppler flow measurements, resonance, hysteroscopy, etc. are usually performed).

Finally, it is interesting to study immunology, study of Natural Killers levels (better in endometrium than in blood), Th1/Th2 population; KIR (Natural Killers Receptors); Interleukins…

Optimal thyroid levels for fertility?

Subclinical hypothyroidism is a frequent cause of repeat miscarriages and implantation failures. The patient is asymptomatic and has normal T4 levels, although the TSH is usually increased.  It is generally accepted that the TSH should be equal to or less than 2, with T4 within the limits of normal before performing fertility treatment.

Evidence of weight loss for obese people and infertility?

It is true that once we are in the range of obesity, the lower the weight the better the fertility, which is widely demonstrated, by mechanisms that are not entirely known. This does not mean under any circumstances that obese people cannot have children or cannot carry out a treatment, simply their chances of success will be lower.  In addition, extremely thin people (anorexia nervosa, malnutrition) also have problems getting pregnant, and sometimes even having regular periods. In short, as in almost every aspect of life, virtue is in the middle ground. The most important thing is keeping your gut health in check, and keeping your body healthy.

How much does it tend to cost?

At IVF-Spain the Im Map test, which is the immunological testing, costs 120€ if it is performed at the first visit at the clinic and 220€ if it is performed at another time.

Why are some people skeptical about Immunology helping fertility?

The collaboration between immunology and reproductive medicine, as explained above, is very new.  Many of the theories postulated have not been able to be absolutely proven, since this requires more time, more patients – in short, more experience.

Today, medical knowledge is based on so-called evidence-based medicine. This way of acquiring scientific knowledge is based on statistics, the part of mathematics that tries to predict facts that do not always occur in the same way.  There are certain statistical techniques that assess the probability that a certain event that seems to be true is simply due to chance.  Since not all people have the same symptoms in the same disease, and since not all drugs act the same way in different individuals (i.e., medical events do not occur the same way in all people), these statistical tests have been applied in medicine to define with high probability what is true and what is not true.  Well, for these tests to work correctly, it is necessary to have a large number of diagnosed cases of the same pathology, which are comparable and have been treated differently under study conditions. Subsequently, it is evaluated whether there are differences in the success achieved between the two groups, and the probability that this is simply due to chance. The greater the difference between the groups and the greater the number of homogeneous cases treated, the greater the probability of finding a difference, even if it is small.

In the case of immunological problems, we find that in general, as we have mentioned before, fairly high pregnancy rates have already been achieved in reproductive medicine using non-immunological techniques. Immunology is therefore in the area of implantation failure and repeat study in which no other diagnosis has been reached. Fortunately, in the context of assisted reproduction in general these cases are few, so there are not many patients who receive diagnoses and treatments of this type. If we count on the fact that due to the youth of these techniques the recruitment time is small, it is easy to understand with what was explained above that the probability that a certain technique solidly demonstrates its effectiveness is still small. Many of the immunological therapies have only demonstrated effectiveness in some studies or in a partial way. So many doctors and patients are still skeptical of all or some of the immune diagnostics and treatments. Time will tell how many and which ones will prove their effectiveness absolutely and in which groups of patients. It is also more than likely that over time we will see the emergence of other diagnostics and therapies still unimaginable today. This is an exciting, new and continually developing field, and like all innovations in medicine it generates a skepticism that is probably healthy.

Does it increase IVF success rates?

In general, few patients are subsidised by complex immunological treatments, and most problems in reproductive medicine can usually be treated with non-immunological therapies. Thus the increase in IVF success rates in the general population is not clearly noticeable.

However, these fertility treatments offer fertility help and hope, and they seem to increase pregnancy rates in patients belonging to certain population groups, mainly in cases of repeated abortions and implantation failures.

How does Immunology work if you’re having treatment abroad?

Medical treatments and diagnostics are not dependent on ethnicity or geography and are easily prescribed and followed from a distance. The fact that they are carried out in a foreign country doesn’t make a difference.

A big thank you to the team at IVF Spain and Dr Rogel for giving us the low-down on immunology and fertility treatment. You can book a virtual FREE consult with the team at IVF Spain HERE.

Hopefully this IVF blog article has given you a deeper insight into IVF Spain and what they do, in addition to answering any questions you may have had about Immunology and Fertility.

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